Inpatient antimicrobial stewardship (AMS) programs have a toolbox of potential interventions to curb inappropriate antibiotic use, prevent antibiotic-associated adverse drug events, and avoid unnecessary costs of care. Fluoroquinolone restriction policies in the acute care setting have demonstrated beneficial effects, including decreased rates of C. difficile infection and ESBL-producing Enterobacteriaceae. However, a simple blanket restriction policy may "squeeze the antibiotic balloon" and will likely be insufficient if not implemented in conjunction with other AMS interventions. There is a growing body of evidence to support formulary restriction of fluoroquinolones in the acute care setting to decrease rates of C. difficile infection and development of ESBL-producing organisms. Data on how to best implement these restrictions or how to implement outside of acute care settings is limited.
Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.
Background: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are increasingly common; however, predicting which patients are likely to be infected with an ESBL pathogen is challenging, leading to increased use of carbapenems. To date, five prediction models have been developed to distinguish between patients infected with ESBL pathogens. The aim of this study was to validate and compare each of these models, to better inform antimicrobial stewardship.
Methods: This was a retrospective cohort study of patients with gram-negative bacteremia treated at the South Texas Veterans Health Care System over 3 months from 2018 to 2019. We evaluated isolate, clinical syndrome, and score variables for the five published prediction models/scores: Italian “Tumbarello”, Duke, University of South Carolina (USC), Hopkins Clinical Decision Tree, and Modified Hopkins. Each model was assessed using the receiver-operating-characteristic curve (AUROC) and Pearson correlation.
Results: 145 patients were included for analysis, of which 20 (13.8%) were infected with an ESBL E. coli or Klebsiella spp. The most common sources of infection were genitourinary (55.8%) and gastrointestinal/intraabdominal (24.1%) and the most common pathogen was E. coli (75.2%). The prediction model with the strongest discriminatory ability (AUROC) was Tumbarello (0.7556). Correlation between prediction model score and percent ESBL was strongest with Modified Hopkins (R2=0.74).
Conclusions: In this veteran population, the Modified Hopkins and Duke prediction models were most accurate in discriminating between gram-negative bacteremia patients when considering both AUROC and correlation. However, given the moderate discriminatory ability, many patients with ESBL Enterobacteriaceae (at least 25%) may still be missed empirically.
Introduction
A pharmacist‐managed area‐under the concentration time curve/minimum inhibitory concentration (AUC/MIC)‐based vancomycin dosing and monitoring strategy was implemented at the University of Maryland Medical Center (UMMC) in January 2017. Because this was a large change in practice and methodology, we sought to understand pharmacists' perceptions of the practice before and after implementation.
Methods
A mixed methods preimplementation survey was sent to all pharmacists, including residents, completing vancomycin dosing training at UMMC 1 month prior to transition to an AUC‐guided pharmacist‐to‐dose practice. The postimplementation survey was subsequently sent 8 months after program rollout to the same study participants.
Results
A total of 127 responses completed the survey: 78 in the preimplementation and 49 in the postimplementation arm. Clinical specialist pharmacists represented 53.8% vs 49.0%, clinical pharmacists represented 32.1% vs 36.7%, and residents represented 14.3% vs 14.1%, respectively. Prior to implementation, 42.3% responded that AUC/MIC was the ideal pharmacokinetic/pharmacodynamic parameter, compared with 93.9% postimplementation (P < 0.0001). Weight‐based dosing was primarily used preimplementation as opposed to postimplementation (46.2% vs 6.1%; P < 0.0001). The average time spent evaluating a vancomycin dose increased from 8 (interquartile range [IQR] 5‐15) minutes to 15 (IQR 10‐17.5) minutes (P < 0.0001). Respondents strongly agreed that pharmacist‐to‐dose AUC/MIC vancomycin for working at the top of their degree (53.1% preimplementation vs 61.5% postimplementation; P = 0.261). Main concerns regarding changes in vancomycin dosing practices included lack of pharmacist competency, which decreased after rollout (48.7% preimplementation vs 24.5% postimplementation; P = 0.081). Before implementation, respondents felt that practice problems and training sessions (69.2%) and computer decision support (57.7%) would be key to a successful rollout. Satisfaction with the rollout increased postimplementation (26.9% vs 49.0%, respectively P = 0.011).
Conclusion
Pharmacists were in support of pharmacist‐to‐dose AUC vancomycin dosing practices, but there were concerns regarding competency. Training sessions with practice problems and integrated clinical decision support improved the rollout process.
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